AHRQ's recent notice regarding Interest in Health Services Research to Address the Opioid Crisis [NOT-HS-18- 015] recognized the alarming disproportionate increase of opioid-related hospitalizations among older adults. Despite an abundance of efforts to combat the national opioid epidemic, hospitalizations due to opioid dependence, abuse or poisoning among older adults have grown disproportionally. To accurately identify the high-risk elderly groups and implement effective preventive measures, it is important to understand the etiology of opioid-related hospitalizations, with a special emphasis on elderly-specific risk factors. This study will assess elderly high-risk prescription opioid use patterns, predisposing and prognostic factors and their associations with opioid-related hospitalizations. To understand the progress from prescription opioid initiation to the development of opioid-related hospitalization outcome, the target population is Medicare beneficiaries who initiate prescription opioids at an older age (aged 65+) included in a nationally representative sample of Medicare beneficiaries from 2001-20017. Our Aim 1 is to examine trajectories of prescription opioid use and their association with opioid-related hospitalizations after initiation among opioid-nave Medicare older adults. Prescription opioid use will be assessed by four measures: 1) morphine-equivalent daily dose, 2) concomitant opioid use, 3) chronic opioid use, and 4) concurrent use with other psychotropic drugs (e.g., benzodiazepines). Our Aim 2 is to examine the extent to which elderly-specific predisposing and prognostic factors are associated with risk for opioid-related hospitalization outcome after opioid initiation among Medicare older adults. We will examine unique risk factors for the development of the outcome, including a frailty index, number of chronic conditions and polypharmacy. Innovative among published models in any population, we will also evaluate emerging prognostic factors? incident infections, cognitive impairment, and injuries, reflecting potential opioid misuse and overdose that lead to hospitalizations. Our study will provide first-hand nationally representative data on trajectories of prescription opioid use, predisposing characteristics and prognostic risk factors associated with opioid-related hospitalizations in elderly opioid initiators. Identified elderly-specific risk factors will provide the foundation for a future R01 aimed at developing, implementing and evaluating a dynamic elderly-specific risk score in clinical practice. The results from this line of research will assist clinicians to identify and manage elderly patients at risk for opioid-related adverse events, improving opioid prescribing and safety in geriatric populations.